This research is an investigation of the biosynthesis of estrogens and other steroid hormones, and the interrelationships between human development and steroid hormones. It aims also to develop useful biochemical and analytical methods of clinical applicability. Our immediate objectives are: (1) to elucidate the steric, kinetic, and electronic mechanisms of aromatization and lyase reaction by steroid hormone synthesizing systems, (2) to isolate and characterize placental aromatases and to delineate the enzyme structures, (3) to isolate protein components (cytochrome P-450 and NADPH-cyt P-450 reductase) of aromatases of human placenta and of other mammals and study the functionality of cross-reconstituted enzyme systems, (4) to produce and characterize antibodies against human aromatase I and II, and their specific component proteins, (5) to develop active-site directed or suicide inhibitors for aromatase, (6) to discover the course of sex steroid synthesizing and metabolizing enzyme activities (aromatase, hydroxylase, dehydrogenase, transferase, etc.) during fetal development in comparison to postnatal stages, (7) to elucidate steroid configurations, conformations and reactivities, and (8) to develop rapid and simple assays of estrogen synthetases and steroid hydroxylases. The methods involve synthesis of steroids with and without deuterium, tritium, carbon-13, carbon-14 and oxygen-18 labels at stereoselective and/or regiospecific positions, conformational analysis by neutron and X-ray crystallography and spectroscopy, chemical and biochemical distribution analysis of isotopes, incubations with various enzyme preparations, enzyme solubilization and purification, antibody production, and physico-chemical and immuno-chemical technology.